| 1. |
|
|
| 2. |
- Menden, MP, et al.
(författare)
-
Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
-
Tidskriftsartikel (refereegranskat)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
|
|
| 3. |
- Gehlot, B. K., et al.
(författare)
-
The first power spectrum limit on the 21-cm signal of neutral hydrogen during the Cosmic Dawn at z=20-25 from LOFAR
- 2019
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 488:3, s. 4271-4287
-
Tidskriftsartikel (refereegranskat)abstract
- Observations of the redshifted 21-cm hyperfine line of neutral hydrogen from early phases of the Universe such as Cosmic Dawn and the Epoch of Reionization promise to open a new window onto the early formation of stars and galaxies. We present the first upper limits on the power spectrum of redshifted 21-cm brightness temperature fluctuations in the redshift range z = 19.8-25.2 (54-68 MHz frequency range) using 14 h of data obtained with the LOFAR-Low Band Antenna (LBA) array. We also demonstrate the application of a multiple pointing calibration technique to calibrate the LOFAR-LBA dual-pointing observations centred on the North Celestial Pole and the radio galaxy 3C220.3, We observe an unexplained excess of similar to 30-50 per cent in Stokes / noise compared to Stokes V for the two observed fields, which decorrelates on greater than or similar to 12 s and might have a physical origin. We show that enforcing smoothness of gain errors along frequency direction during calibration reduces the additional variance in Stokes I compared Stokes V introduced by the calibration on sub-band level. After subtraction of smooth foregrounds, we achieve a 2 sigma upper limit on the 21-cm power spectrum of Delta(2)(21) < (14561 mK)(2) at k similar to 0.038 h cMpc(-1) and Delta(2)(21) < (14886 mK)(2) at k 0.038 h cMpc(-1) for the 3C220 and NCP fields respectively and both upper limits are consistent with each other. The upper limits for the two fields are still dominated by systematics on most k modes.
|
|
| 4. |
- Grohs, Melody N., et al.
(författare)
-
Prenatal maternal and childhood bisphenol a exposure and brain structure and behavior of young children
- 2019
-
Ingår i: Environmental Health. - : Springer Science and Business Media LLC. - 1476-069X. ; 18:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Bisphenol A (BPA) is commonly used in the manufacture of plastics and epoxy resins. In North America, over 90% of the population has detectable levels of urinary BPA. Human epidemiological studies have reported adverse behavioral outcomes with BPA exposure in children, however, corresponding effects on children's brain structure have not yet been investigated. The current study examined the association between prenatal maternal and childhood BPA exposure and white matter microstructure in children aged 2 to 5 years, and investigated whether brain structure mediated the association between BPA exposure and child behavior.Methods: Participants were 98 mother-child pairs who were recruited between January 2009 and December 2012. Total BPA concentrations in spot urine samples obtained from mothers in the second trimester of pregnancy and from children at 3-4 years of age were analyzed. Children participated in a diffusion magnetic resonance imaging (MRI) scan at age 2-5 years (3.7 +/- 0.8 years). Associations between prenatal maternal and childhood BPA and children's fractional anisotropy and mean diffusivity of 10 isolated white matter tracts were investigated, controlling for urinary creatinine, child sex, and age at the time of MRI. Post-hoc analyses examined if alterations in white matter mediated the relationship of BPA and children's scores on the Child Behavior Checklist (CBCL).Results: Prenatal maternal urinary BPA was significantly associated with child mean diffusivity in the splenium and right inferior longitudinal fasciculus. Splenium diffusivity mediated the relationship between maternal prenatal BPA levels and children's internalizing behavior (indirect effect: beta = 0.213, CI [0.0167, 0.564]). No significant associations were found between childhood BPA and white matter microstructure.Conclusions: This study provides preliminary evidence for the neural correlates of BPA exposure in humans. Our findings suggest that prenatal maternal exposure to BPA may lead to alterations in white matter microstructure in preschool aged children, and that such alterations mediate the relationship between early life exposure to BPA and internalizing problems.
|
|
| 5. |
- Kooistra, Robin, et al.
(författare)
-
Radial decoupling of small and large dust grains in the transitional disk RX J1615.3-3255
- 2017
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 597
-
Tidskriftsartikel (refereegranskat)abstract
- We present H-band (1.6 mu m) scattered light observations of the transitional disk RX J1615.3-3255, located in the similar to 1 Myr old Lupus association. From a polarized intensity image, taken with the HiCIAO instrument of the Subaru Telescope, we deduce the position angle and the inclination angle of the disk. The disk is found to extend out to 68 +/- 12 AU in scattered light and no clear structure is observed. Our inner working angle of 24 AU does not allow us to detect a central decrease in intensity similar to that seen at 30 AU in the 880 mu m continuum observations. We compare the observations with multiple disk models based on the spectral energy distribution (SED) and submm interferometry and find that an inner rim of the outer disk at 30 AU containing small silicate grains produces a polarized intensity signal which is an order of magnitude larger than observed. We show that a model in which the small dust grains extend smoothly into the cavity found for large grains is closer to the actual H-band observations. A comparison of models with di ff erent dust size distributions suggests that the dust in the disk might have undergone significant processing compared to the interstellar medium.
|
|
| 6. |
- McNamee, Sara E., et al.
(författare)
-
Distribution, occurrence and biotoxin composition of the main shellfish toxin producing microalgae within European waters : A comparison of methods of analysis
- 2016
-
Ingår i: Harmful Algae. - : Elsevier BV. - 1568-9883 .- 1878-1470. ; 55, s. 112-120
-
Tidskriftsartikel (refereegranskat)abstract
- Harmful algal blooms (HABs) are a natural global phenomena emerging in severity and extent. Incidents have many economic, ecological and human health impacts. Monitoring and providing early warning of toxic HABs are critical for protecting public health. Current monitoring programmes include measuring the number of toxic phytoplankton cells in the water and biotoxin levels in shellfish tissue. As these efforts are demanding and labour intensive, methods which improve the efficiency are essential. This study compares the utilisation of a multitoxin surface plasmon resonance (multitoxin SPR) biosensor with enzyme-linked immunosorbent assay (ELISA) and analytical methods such as high performance liquid chromatography with fluorescence detection (HPLC-FLD) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for toxic HAB monitoring efforts in Europe. Seawater samples (n = 256) from European waters, collected 2009-2011, were analysed for biotoxins: saxitoxin and analogues, okadaic acid and dinophysistoxins 1/2 (VDU /DTX2) and domoic acid responsible for paralytic shellfish poisoning (PSP), diarrheic shellfish poisoning (DSP) and amnesic shellfish poisoning (ASP), respectively. Biotoxins were detected mainly in samples from Spain and Ireland. France and Norway appeared to have the lowest number of toxic samples. Both the multitoxin SPR biosensor and the RNA microarray were more sensitive at detecting toxic HABs than standard light microscopy phytoplankton monitoring. Correlations between each of the detection methods were performed with the overall agreement, based on statistical 2 x 2 comparison tables, between each testing platform ranging between 32% and 74% for all three toxin families illustrating that one individual testing method may not be an ideal solution. An efficient early warning monitoring system for the detection of toxic HABs could therefore be achieved by combining both the multitoxin SPR biosensor and RNA microarray. (C) 2016 Elsevier B.V. All rights reserved.
|
|
